Our objective is to elucidate the mechanism of regression of hormone-responsive mammary and lymphoid tumors after withdrawal of hormone support (mammary tumor MTW9) or following glucocorticoid treatment (mouse lymphoma P1798) both in vivo and in vitro. We will investigate the mechanism and role of hormone-induced changes in small molecule (amino acid, nucleosides, sugars, ions) transport in tumor regression, in conjunction with effects on induction or repression of specific classes of RNA and protein essential for these processes. Regulation of mammary tumor growth will be studied by examining interactions among estradiol, progesterone, prolactin and insulin, and resection of supporting tumor MtTW5 (model for hypophysectomy-induced regression of breast cancer in humans) on the binding capacity of specific hormone receptors and on tumor RNA, DNA and protein synthesis. We will explore the role of insulin, prostaglandins, catecholamines and cyclic nucleotides in glucocorticoid-induced resorption of malignant lymphoid tissue. The biochemistry of resistance to hormonal therapy will be investigated in autonomous strains of mammary tumor and in corticoid-resistant sublines of lymphoma P1798. These studies will involve examination of the role of nuclear acidic proteins and histones, enzymic and chemical modification of the plasma membrane and specific changes in hormone receptors. Attempt will be made to convert resistant cells to the sensitive state, and vice versa, under carefully controlled condition so as to pinpoint the locus of hormone resistance.